Diisopropylethylamine → HCID 74220581, compound

HRID 1509048Notes

Reaction equation

HRID 1509048 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21](O)=[O:22])=[CH:16][CH:15]=3)[C:10]([CH2:24][CH3:25])=[C:9]([CH3:26])[N:8]=2)=[CH:4][CH:3]=1.C[N:28]([C:30](ON1N=NC2C=CC=NC1=2)=[N+:31](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([NH:31][C:30]#[N:28])=[O:22])=[CH:16][CH:15]=3)[C:10]([CH2:24][CH3:25])=[C:9]([CH3:26])[N:8]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15951010HCID 15951010, compound

Product 1

HCID 74220581HCID 74220581, compoundYield 50.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 8-mL vial was charged with 2-[4-[[2-(5-chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]phenyl]acetic acid (30 mg, 0.077 mmol, 1 eq.), cyamide (30 mg, 0.71 mmol, 9 eq.), HATU (44 mg, 0.16 mmol, 1.5 eq.), diisopropylethylamine (35 mg, 0.27 mmol, 3.5 eq.) and DMF (0.5 ml). The resulting mixture was stirred at rt overnight until the starting acid was consumed. The mixture was added to NaHCO3 aq. (5 ml) and extracted with ethyl acetate (5 ml×3). The organic layers were combined and dried over Na2SO4. Removal of solvent gave a residue, which was purified by chromatography on silica gel using 0.5˜3% of MeOH in DCM as eluent to give the title compound as a white solid (16 mg, 50% yield). MW=411.91. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (brs, 1H), 7.67 (d, J=8.8 Hz, 2H), 7.55 (d, J=4.0 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.15 (d, J=4.0 Hz, 1H), 5.77 (s, 2H), 2.74 (q, J=7.6 Hz, 2H), 2.40 (s, 3H), 1.20 (t, J=7.6 Hz, 3H).

Workup

  1. customwas consumed
  2. additionThe mixture was added to NaHCO3 aq. (5 ml)
  3. extractionextracted with ethyl acetate (5 ml×3)
  4. dry with materialdried over Na2SO4
  5. customRemoval of solvent
  6. customgave a residue, which
  7. customwas purified by chromatography on silica gel using 0.5˜3% of MeOH in DCM as eluent

Sources & evidence

ORD record
ord-5c4d15a81ccf49838e0cc8d2ff5a6a2a
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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